Alternans Resonance and Propagation Block during Supernormal Conduction in Cardiac Tissue with Decreased [K+]o

Abstract

Cardiac restitution is an important factor in arrhythmogenesis. Steep positive action potential duration and conduction velocity (CV) restitution slopes promote alternans and reentrant arrhythmias. We examined the consequences of supernormal conduction (characterized by a negative CV restitution slope) on patterns of conduction and alternans in strands of Luo-Rudy model cells and in cultured cardiac cell strands. Interbeat intervals (IBIs) were analyzed as a function of distance during S1S2 protocols and during pacing at alternating cycle lengths. Supernormal conduction was induced by decreasing [K(+)](o). In control [K(+)](o) simulations, S1S2 intervals converged toward basic cycle length with a length constant determined by both CV and the CV restitution slope. During alternant pacing, the amplitude of IBI alternans converged with a shorter length constant, determined also by the action potential duration restitution slope. In contrast, during supernormal conduction, S1S2 intervals and the amplitude of alternans diverged. This amplification (resonance) led to phase-locked or more complex alternans patterns, and then to distal conduction block. The convergence/divergence of IBIs was verified in the cultured strands, in which naturally occurring tissue heterogeneities resulted in prominent discontinuities of the spatial IBI profiles. We conclude that supernormal conduction potentiates alternans and spatial analysis of IBIs represents a powerful method to locate tissue heterogeneities.

Supernormal conduction in cardiac tissue promotes concordant alternans and action potential bunching

“…Our results are highly relevant to excitable media and to all experiments where SNC is found in cardiac tissue (see, e.g., Ref. [13]). With respect to alternans, the experimental observation of straight defect lines in period-doubled spirals in cell cultures of cardiac rat cells [21] …”

“…SNC is found, for example, in the Iyer-Mazhari-Winslow [9] or in the Drouhard-RobergeBeeler-Reuter (DRBR) model [10,11] employed in the study here, and it is often observed under conditions of low extracellular potassium concentration [12]. Recently, it has been shown to potentiate the onset of alternans in cultured cardiac cell strands [13] and also in generic models of spiral wave formation [14].Alternans is an oscillation in the duration of the AP that usually occurs at short stimulation periods [15]. In a paced cable or tissue alternans appears in two major forms, concordant (CA) and discordant (DA) alternans, depending on if the phase of the alternation is the same along the tissue or it presents nodes (in 1D) or nodal lines (in 2D) separating regions of tissue oscillating out of phase.…”

“…SNC is found, for example, in the Iyer-Mazhari-Winslow [9] or in the Drouhard-RobergeBeeler-Reuter (DRBR) model [10,11] employed in the study here, and it is often observed under conditions of low extracellular potassium concentration [12]. Recently, it has been shown to potentiate the onset of alternans in cultured cardiac cell strands [13] and also in generic models of spiral wave formation [14].…”

A Discrete Electromechanical Model for Human Cardiac Tissue: Effects of Stretch-Activated Currents and Stretch Conditions on Restitution Properties and Spiral Wave Dynamics

“…It has been shown that abnormal CV restitution can cause alternans and initiation of spiral waves [49], [50], and also important phenomena on spiral wave dynamics such as discordant alternans can be caused by abnormal CV restitution [51], [52]. We expect that this mechanism of mechanically caused abnormal CV-restitution is important to understand the onset of arrhythmias due to emergent dynamic inhomogeneities.…”

Myofibroblasts Electrotonically Coupled to Cardiomyocytes Alter Conduction: Insights at the Cellular Level from a Detailed In silico Tissue Structure Model

“…This initial increase was attributed to supernormal conduction, whereby the initial slight depolarization by a low number of MFBs brings the RMP of CMCs closer to the threshold of I Na activation (thus accelerating conduction), whereas further RMP depolarization causes partial I Na inactivation (thus slowing conduction). While our CMC model (based on Luo-Rudy I Na dynamics) can reproduce supernormal conduction caused, e.g., by a change of [ K + ] o (Luo and Rudy, 1991; de Lange and Kucera, 2009, 2010), it failed to reproduce supernormal conduction caused in experiments by a small density of MFBs (Miragoli et al, 2006). This observation is not surprising, since our model is characterized by a high coupling regime (see above).…”